Modulation of T cells in a murine breast cancer model developed in histamine H4 receptor deficient mice

MELISA N NICOUD; MONICA TAQUEZ DELGADO; MARÍA DE LA PAZ SARASOLA; DANIELA SPEISKY; GRACIELA CREMASCHI; HELENA STERLE; VANINA A MEDINA

Congreso; LXV Reunión Anual de la SAIC, Sociedad Argentina de Investigación Clínica; 2020

The histamine H4 receptor (H4R) is preferentially expressed in immune cells and is a potential therapeutic target for inflammatory and autoimmune diseases. This study aimed at further exploring the role of H4R in the immunobiology of breast cancer.We used wild type (WT) and H4R deficient (H4R-KO) Balb/c mice to evaluate whether H4R genotypes show different distribution of T cell subsets in spleens, tumours and tumour draining lymph nodes (TDLN) in a syngeneic ErbB2-positive breast cancer model developed orthotopically with LM3 cells and its impact on tumour growth. In addition, the migration capacity of TDLN cells from WT and KO animals was analyzed.The presence of tumours had a differential impact on the distribution of T cells in TDLN from H4R-KO mice compared to WT ones. At day 21 post inoculation (p.i.) of cells, despite no significant changes in the tumour weight, TDLN from H4R-KO mice showed a significantly increased proportion of CD8+ T cells compared to WT mice (P=0.0052). At day 38 p.i. of cells a reduced tumour weight was evident in H4R-KO mice (P=0.0431). This was accompanied by a decreased proportion of CD4+CD25+FoxP3+ regulatory T cells in TDLN of KO compared to WT mice (P=0.0104). In agreement with the tumour weights, the spleen weight was significantly reduced in tumour-bearing KO mice compared with WT counterparts (P=0.0280). Tumour-bearing KO mice showed a better survival compared to WT mice (P=0.0511). Furthermore, H4R deficient TDLN lymphocytes showed impaired chemotaxis compared with WT mice (P=0.0054).We conclude that H4R-mediated mechanisms may modulate the immune tumour microenvironment, promoting an immunosuppressive milieu. Results suggest that H4R could be explored as an immunotherapeutic target with potential benefit in combination with immunotherapy.